Objective: To report a clinical and genetic study of a large family with febrile seizures (FS) and childhood absence epilepsy (CAE).
Methods: This family was identified through a French campaign for familial epilepsies. It spans four generations and consists of 51 members, 13 of whom were affected. The medical history of all members was obtained by personal information and by consulting the medical files of affected members. All family members gave written consent to participate in the study.
Results: All affected members presented FS, with CAE in five and temporal lobe epilepsy (TLE) in one. FS stopped before age 6 years in all but one patient. FS were simple, except in one patient who had a long-lasting complex FS at 8 months of age. He later presented pharmacoresistant TLE and left hippocampal sclerosis was visible on brain MRI. Patients presenting CAE had recorded absences and characteristic EEGs with 3 Hz spike waves. After exclusion of reported loci for FS and generalized epilepsy with FS plus, a genome-wide search allowed us to map a new locus for FS on 3p. We could not exclude another genomic segment on chromosome 18p and all patients presenting epilepsy (CAE and TLE) shared a common haplotype at this locus in addition to the haplotype on 3p.
Conclusion: These findings emphasize the genetic heterogeneity of febrile seizures. Furthermore, epilepsy in association with febrile seizures might result in this family from an interaction between at least two genes: the gene on 3p and a possible modifier gene on 18p.